Diabetes Research and Clinical Practice, 18 (1992) 75-81 0 1992 Elsevier Science Publishers
75
B.V. All rights reserved 0168-8227/92/$05.00
DIABET 00677
Diabetic nephropathy: duplex Doppler ultrasound findings Seung
Hyup
Kim”,
Sung Moon
Kim a, Hong Kyu Leeb, Suhnggwon and Man Chung Han”
Kim b, Jung
Sang Lee a
Departments of a Radiology and b Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul 11 O-744, Korea
(Received 6 January 1992) (Revision accepted 2 May 1992)
Summary To evaluate the correlations among Doppler sonographic findings, morphologic sonographic findings, and laboratory findings representing renal functional status, duplex Doppler sonography of the kidney was performed in 32 patients with diabetes mellitus. Resistive indices obtained in the region of the arcuate or the interlobar arteries in patients with elevated serum creatinine levels were significantly higher than those in patients with normal serum creatinine levels (PcO.05). Also, there was a significant correlation between the resistive indices and creatinine clearance levels (correlation coefficient, -0.828). There was a significant difference between the serum creatinine levels of patients with normal renal cortical echogenicity and those with increased cortical echogenicity (PC 0.05). Analysis of the Doppler spectrum of the intrarenal arteries in conjunction with careful evaluation of the renal cortical echogenicity may be helpful in sonographic prediction of the renal functional status in patients with diabetes mellitus. Key words: Diabetes mellitus; Kidney, diseases; Ultrasound, Doppler studies
Introduction Diabetic nephropathy is the most important single disorder leading to renal failure in adults and 40-45x of insulin-dependent patients will develop diabetic nephropathy [ 11. Although it is well known that diabetes mellitus is a prominent Correspondence to: Seung Hyup Kim, Department of Radiology, Seoul National University Hospital, 28 Yongon-Dong, Chongno-Gu, Seoul 110-744, Korea.
Kidney,
parenchymal
pattern;
Kidney,
US studies;
cause of bilateral renomegaly [ 2,3], there has been no established sonographic criteria which allows differentiation between functionally preserved kidneys and functionally impaired ones in a diabetic patient. The main histopathologic features of the kidneys involved in diabetes mellitus, i.e. diffuse glomerulosclerosis along with arteriosclerotic changes [ 1,4], may cause elevated peripheral renal vascular resistance, which can be demonstrated by changes in the Doppler spectrum of the renal arterial system.
76
This prospective study was designed to evaluate the correlation among Doppler spectra obtained at the arculate or interlobar arteries of the kidney, morphologic ultrasound findings of the kidney, and blood/urine findings representing renal functional status in diabetic patients
Materials and Methods Duplex Doppler ultrasound of the kidneys was performed in 32 patients (16 males and 16 females) with diabetes mellitus. The age of these patients ranged from 24 to 72 years (mean, 58 years). The history of diabetes mellitus in these patients ranged from 1 to 25 years with a mean of 10.9 years. The patients were being managed with
Fig. l(a).
dietary control in three, with oral medications in 14, with insulin injection in 11, and with combined oral medications and insulin injection in four patients. The sonogram of both kidneys was obtained with a 3.5 MHz convex transducer and the duplex Doppler examination was performed with a 2.0 MHZ mechanical sector transducer (Aloka SSD 650). The Doppler signal was taken in the area of the arcuate or the interlobar arteries. From the sonographic images of both kidneys, renal length was measured, and the echogenicity of the cortex was classified into four groups as follows [5]: Grade 0 (normal. The echogenicity of the cortex of the right kidney was less than that of the liver); Grade 1 (the echogenicity of the cortex of the right kidney equalled that of the liver); Grade 2
For legend,
see p. 7X
77
(the echogenicity of the cortex of the right kidney was greater than that of the liver, but less than that of the renal sinus); Grade 3 (the echogenicity of the renal cortex was equal to that of the renal sinus). Corticomedullary contrast was graded subjectively as follows [ 61: Grade 0 (no corticomedullary definition); Grade 1 (poorly defined medulla); Grade 2 (normal corticomedullary definition); Grade 3 (enhanced corticomedullary definition). From the Doppler spectra, the resistive index [(systolic frequency shift - diastolic frequency shift)/systolic frequency shift] was calculated. The resistive index was obtained from three different areas on each kidney and the average value was taken. The length of time devoted to the examination of each patient was 20-30 min. All the
ultrasound examinations were performed without knowledge of the laboratory findings of the patients. The time interval between the sampling of blood or urine for laboratory examination and ultrasound examination was less than 3 days. Resistive index, renal length, renal cortical echogenicity, and the degree of cortico-medullary contrast were compared with serum creatinine level, and the statistical significances of those correlations were evaluated by t-test. In patients with a normal level of serum creatinine, we evaluated the correlation between resistive index and albuminuria (albustix-positive) using Wilcoxon rank sum test. In 23 patients for whom the data for creatinine clearance were available, resistive index was compared with creatinine clearance level using a regression analysis.
Fig. l(b). For legend, see p. 78.
78
Fig. 1. Duplex Doppler sonograms of the kidney in patients with diabetes mellitus. (a) A 45-year-old female patient with a history of diabetes mellitus for 7 years being managed by oral medications. The Doppler spectrum obtained in the region of an arcuate artery shows prominent continuous antegrade flow throughout the diastolic phase with a resistive index of 0.722. Her serum creatinine level was 88.4 pmol/l (1 .O mg/dl) and creatinine clearance was 58 ml/min. Doppler spectral analysis was performed on the spectrum below the baseline. (b) A 69-year-old female patient with a history of diabetes for 10 years being managed by self injection of insulin for 4 years. The Doppler spectrum obtained in the region of an interlobar artery shows diminished, but still continuous, antegrade flow throughout the diastolic phase with a resistive index of 0.777. Her serum creatinine level was 344.8 pmol/l (3.9 mg/dl) and creatinine clearance was 10 ml/n% (c) A 52-year-old male patient with a history of diabetes for 10 years being managed by oral medications. The Doppler spectrum obtained in the region of an interlobar artery shows complete loss of enddiastolic flow, resulting in a resistive index of 1.0. His serum creatinine level was 556.9 pmol/l (6.3 mg/dl) and creatinine clearance was 12 ml/min.
Results There were 18 patients with a normal serum creatinine level (< 1.4 mg/dl) and 14 patients with an elevated serum creatinine level (> 1.4 mg/dl) up to 13.7 mg/dl. Resistive indices of Doppler spectra obtained from arcuate or interlobar arteries of the kidneys of patients with a normal serum creatinine level were between 0.56 and 0.82 with a
mean of 0.69 (Fig. la). In patients with an elevated serum creatinine level, resistive indices were between 0.72 and 1.0 with a mean of 0.92 (Fig. lb,c). There was a statistically significant difference between resistive indices in diabetic patients with a normal serum creatinine level and those in diabetic patients with an elevated serum creatinine level (P~0.05) (Fig. 2). If we use a resistive index of 0.75 as a cut-off value for pre-
79
DM Nephropathy Serum creatinine
DM Nephropathy
vs Resistive Index
Creatinine Clearance vs Resistive Index 100
.
90. r 'E 3 ig 8 6 f" 0 0 .5 5 s! 6
90--
*..A
A .A
70- .... 60.
a--
*;_ AA
*
*r.&A...
m_
A. *
20.
* ;..
IO-OT 0.5
0.6
0.7
0.8
0.9
1
1.1
Fmidive Index
Fig. 2. Serum creatinine versus resistive index in patients with diabetes mellitus. As the serum creatinine level increases, resistive index also increases.
Fig. 3. Creatinine clearance versus resistive index in patients with diabetes mellitus. As the creatinine clearance decreases, resistive index increases.
dieting an abnormal serum creatinine level, it has a sensitivity of 93 %, a specificity of 83 %, an accuracy of 88 %, a positive predictive value of 8 1%) and a negative predictive value of 94% (13 truepositives, three false-positives, 1.5 true-negatives, and one false-negative). In 23 patients for whom data of creatinine clearance were available, the resistive index also correlated well with creatinine clearance level on regression analysis with a correlation coefficient of -0.828, which was statistically significant at the 95% confidence level (Fig. 3). Among 18 patients with a normal serum creatinine level, urine albumin was positive in four patients and negative in 14 patients. In 14 patients with normal serum creatinine and negative urine albumin, resistive indices were between 0.56 and 0.81 with a mean of 0.68. In four patients with a normal serum creatinine level and positive urine albumin, resistive indices were between 0.70 and 0.82 with a mean of 0.75. In those diabetic patients with a normal serum creatinine level, there was no statistically significant difference between resistive index in patients with negative urine albumin and resistive index in patients with postive urine albumin (P = 0.16). The cortical echogenicity of the renal cortex was normal (grade 0) in 17 patients and equal to that of the liver (grade 1) in 15 patients. There
was no case for whom renal cortical echogenicity was higher than that of the liver. The serum creatinine level in patients with normal cortical echogenicity was 1.27 + 0.95 mg/dl (mean + one standard deviation) and 4.96 +_3.42 mg/dl in those for whom the cortical echogenicity was equal to that of the liver. There was a statistically significant difference between the serum creatinine level of patients with normal renal cortical echogenicity and those of patients with increased cortical echogenicity (P~0.05). If we regard an abnormal renal cortical echogenicity as a sign of abnormal serum creatinine level, it has a sensitivity of 86 %, a specificity of 83 %, an accuracy of 84%, a positive predictive value of SO%, and a negative predictive value of 88% (12 truepositives, three false-positives, 15 true-negatives, and two false-negatives). There was no case in which corticomedullary contrast was abnormally enhanced (grade 3) or completely obliterated (grade 0). In 14 cases, corticomedullary contrast was normal (grade 2) and in 18 cases corticomedullary contrast was poorly present (grade 1). When we compared the corticomedullary contrast and serum creatinine level, there was no statistically significant correlation. The average length of both kidneys was between 9.2 and 13.3 cm with a mean of 10.7 cm. In patients in whom serum creatinine was nor-
80
DM Nephropathy Serum creatinine vs Kidney Length
Fig. 4. Serum
creatinine
was no significant
versus
correlation
length
between
and kidney
of the kidney. serum
creatinine
There level
length.
mal, renal length was 10.85 + 0.88 cm, and it was 10.49 k 0.97 cm in patients with abnormal serum creatinine. There was no significant correlation between the length of the kidney and serum creatinine level in patients with diabetes mellitus (P = 0.28) (Fig. 4).
Discussion The kidney is involved in diabetes mellitus in different ways, including diabetic intercapillary glomerulosclerosis, arteriosclerotic changes, glycogen accumulation in the renal tubular epithelium, and acute and chronic pyelonephritis [ 1,4]. Thickening of the basement membranes of the glomerular capillaries and mesangial expansion, which in association with arteriosclerotic changes, may increase renal vascular resistance. These changes in structure are already present very early in the course of diabetic kidney disease and manifest clinically as renal hypertrophy, glomerular hyperfiltration, and sometimes microalbuminuria. In the late stage of the disease, overt (dipstick-positive) proteinuria appears and the patient falls into end-stage renal failure [ 11. It has been reported that diabetes mellitus is one of the numerous causes of bilaterally enlarged kidneys. Excessive glycoprotein deposition result-
ing in enlargement of the glomeruli and the presence of a renotrophic factor such as growth hormone are suggested as possible causes of the renal enlargement in diabetes mellitus [2,3]. However, to our best knowledge, there has been no radiological report written in English regarding the sonographic or Doppler spectral criteria which can predict the functional status of the kidneys in a patient with diabetes mellitus. In our study, renal length was compared with serum creatinine level, and there was no significant correlation between the size of the kidney and the functional status of the kidney. There was a poor correlation between the degree of corticomedullary contrast on ultrasound images and serum creatinine level. Although it has generally been considered that renal cortical echogenicity is neither sensitive nor specific for renal disease [ 71, a few reports opposed that opinion. Rosenfield and Siegel reported that there was a definite relation between cortical echogenicity and the severity of interstitial changes on renal biopsy [ 61. In another report by Choyke et al., renal cortical echogenicity correlated well with severity of the disease in patients with hemolytic uremic syndrome [ 81. In our study, renal cortical echogenicity was a relatively accurate index of the functional status of the kidney in patients with diabetes mellitus. Recently, duplex Doppler sonography has been used in native kidneys with medical renal diseases with promising results [ 9-131. In a report by Patriquin et al., they illustrated an excellent correlation between intrarenal Doppler spectral changes and clinical course of their patients with hemolytic-uremic syndrome [ lo]. This excellent correlation could be explained by the fact that underlying renal changes in hemolytic-uremic syndrome consist of vascular lesions that include microvascular thrombosis and endothelial swelling, which directly affects the degree ofrenal blood flow impairment. Likewise in diabetic kidneys, main pathologic changes affect the circulatory apparatus of the kidney, the glomerular and peritubular capillaries, the arterioles of the glomerulus, and the medium and small arteries of the kidney. Those pathologic changes include intercapillary
81
glomerulosclerosis and arteriosclerotic changes. Doppler spectral changes in a diabetic patient probably reflect the status of the intrarenal blood flow and glomerular filtration. Resistive index is a commonly used angleindependent index representing peripheral vascular impedance [ 131. When the end-diastolic flow signal is absent, the resistive index is 1.0. If the direction of the end-diastolic flow is reversed, the resistive index becomes greater than 1.0. Recently, the primary authors of this article have reported a positive correlation between resistive index and serum creatinine level in patients with medical renal disease and in normal controls [ 131, in which the resistive index of the normal control group was 0.627 & 0.042. Proteinuria is regarded as one of the bad prognostic signs in patients with diabetes mellitus [ I] _ Although in our study resistive index in patients with a normal serum creatinine level and negative urine albumin was not significantly different from that in patients with a normal serum creatinine level and positive urine albumin, further study will be necessary in this respect. In conclusion, analysis of the Doppler spectrum of the intrarenal arteries in conjunction with careful evaluation of the renal cortical echogenicity might be helpful in sonographic differentiation of kidneys with preserved function and those with impaired function in patients with diabetes mellitus.
References 1 Morgensen, C.E., Mauer, S.M. and Kjellstrand, C.M. (1988) Diabetic nephropathy. In: R.W. Schrier and C.W.
2
3 4
5
6
7
8
9
10
11 12
13
Gottschalk (Eds.), Diseases of the Kidney, 4th edn., Vol. 3. Little, Brown and Company, Boston. MA, pp. 2395-2431. Segel, M.C., Lecky, J.W. and Slasky, B.S. (1984) Diabetes mellitus: the prominent cause of bilateral renal enlargement. Radiology 153, 341-342. Kahn, C.B., Raman, P.G. and Zic. Z. (1974) Kidney size in diabetes mellitus. Diabetes 23. 788-792. Jones, D.B. (1985) Kidneys. In: J.M. Kissane (Ed.), Anderson’s Pathology, 8th edn., Vol. 2, C.V. Mosby, St Louis, MO, pp. 754-755. Hricak, H., Cruz, C., Romanski, R. et al. (1982) Renal parenchymal disease: sonographic-histologic correlation. Radiology 144. 141-147. Rosenfield. A.T. and Siegel, N.J. (198 1) Renal parenchyma1 disease: histopathologic-sonographic correlation. AJR 137, 793-798. Platt, J.F.. Rubin, J.M., Bowerman, R.A. and Marn, C.S. (1988)The inability to detect kidney disease on the basis of echogenicity. AJR 151, 317-319. Choyke, P.L., Grant, E.G.. Hoffer, F.A., Tina. L. and Korec, S. (1988) Cortical echogenicity in the hemolytic uremic syndrome: clinical correlation. J. Ultrasound Med. 7, 439-442. Wong. S.N., Lo, R.N.S. and Yu, E.C.L. (1989) Renal blood flow pattern by noninvasive Doppler ultrasound in normal children and acute renal failure patients. J. Ultrasound Med. 8, 135-141. Patriquin. H.B., O’Regan, S., Robitaille, P. and Paltiel, H. (1989) Hemolytic-uremic syndrome: intrarenal arterial Doppler patterns as a useful guide to therapy. Radiology 172, 625-628. Keller, M.S. (1989) Renal Doppler sonography in infants and children. Radiology 172, 603-604. Platt, J.F., Ellis, J.H., Rubin, J.M., DiPietro, M.A. and Sedman, A.B. (1990) Intrarenal arterial Doppler sonography in patients with nonobstructive renal disease: correlation of resistive index with biopsy findings. AJR 154, 1223-1227. Kim, S.H., Kim, W.H., Choi, B.I. and Kim, C.W. (1992) Duplex Doppler US in patients with medical renal disease: resistive index vs serum creatinine level. Clin. Radiol. 45. 85-87.
75
B.V. All rights reserved 0168-8227/92/$05.00
DIABET 00677
Diabetic nephropathy: duplex Doppler ultrasound findings Seung
Hyup
Kim”,
Sung Moon
Kim a, Hong Kyu Leeb, Suhnggwon and Man Chung Han”
Kim b, Jung
Sang Lee a
Departments of a Radiology and b Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul 11 O-744, Korea
(Received 6 January 1992) (Revision accepted 2 May 1992)
Summary To evaluate the correlations among Doppler sonographic findings, morphologic sonographic findings, and laboratory findings representing renal functional status, duplex Doppler sonography of the kidney was performed in 32 patients with diabetes mellitus. Resistive indices obtained in the region of the arcuate or the interlobar arteries in patients with elevated serum creatinine levels were significantly higher than those in patients with normal serum creatinine levels (PcO.05). Also, there was a significant correlation between the resistive indices and creatinine clearance levels (correlation coefficient, -0.828). There was a significant difference between the serum creatinine levels of patients with normal renal cortical echogenicity and those with increased cortical echogenicity (PC 0.05). Analysis of the Doppler spectrum of the intrarenal arteries in conjunction with careful evaluation of the renal cortical echogenicity may be helpful in sonographic prediction of the renal functional status in patients with diabetes mellitus. Key words: Diabetes mellitus; Kidney, diseases; Ultrasound, Doppler studies
Introduction Diabetic nephropathy is the most important single disorder leading to renal failure in adults and 40-45x of insulin-dependent patients will develop diabetic nephropathy [ 11. Although it is well known that diabetes mellitus is a prominent Correspondence to: Seung Hyup Kim, Department of Radiology, Seoul National University Hospital, 28 Yongon-Dong, Chongno-Gu, Seoul 110-744, Korea.
Kidney,
parenchymal
pattern;
Kidney,
US studies;
cause of bilateral renomegaly [ 2,3], there has been no established sonographic criteria which allows differentiation between functionally preserved kidneys and functionally impaired ones in a diabetic patient. The main histopathologic features of the kidneys involved in diabetes mellitus, i.e. diffuse glomerulosclerosis along with arteriosclerotic changes [ 1,4], may cause elevated peripheral renal vascular resistance, which can be demonstrated by changes in the Doppler spectrum of the renal arterial system.
76
This prospective study was designed to evaluate the correlation among Doppler spectra obtained at the arculate or interlobar arteries of the kidney, morphologic ultrasound findings of the kidney, and blood/urine findings representing renal functional status in diabetic patients
Materials and Methods Duplex Doppler ultrasound of the kidneys was performed in 32 patients (16 males and 16 females) with diabetes mellitus. The age of these patients ranged from 24 to 72 years (mean, 58 years). The history of diabetes mellitus in these patients ranged from 1 to 25 years with a mean of 10.9 years. The patients were being managed with
Fig. l(a).
dietary control in three, with oral medications in 14, with insulin injection in 11, and with combined oral medications and insulin injection in four patients. The sonogram of both kidneys was obtained with a 3.5 MHz convex transducer and the duplex Doppler examination was performed with a 2.0 MHZ mechanical sector transducer (Aloka SSD 650). The Doppler signal was taken in the area of the arcuate or the interlobar arteries. From the sonographic images of both kidneys, renal length was measured, and the echogenicity of the cortex was classified into four groups as follows [5]: Grade 0 (normal. The echogenicity of the cortex of the right kidney was less than that of the liver); Grade 1 (the echogenicity of the cortex of the right kidney equalled that of the liver); Grade 2
For legend,
see p. 7X
77
(the echogenicity of the cortex of the right kidney was greater than that of the liver, but less than that of the renal sinus); Grade 3 (the echogenicity of the renal cortex was equal to that of the renal sinus). Corticomedullary contrast was graded subjectively as follows [ 61: Grade 0 (no corticomedullary definition); Grade 1 (poorly defined medulla); Grade 2 (normal corticomedullary definition); Grade 3 (enhanced corticomedullary definition). From the Doppler spectra, the resistive index [(systolic frequency shift - diastolic frequency shift)/systolic frequency shift] was calculated. The resistive index was obtained from three different areas on each kidney and the average value was taken. The length of time devoted to the examination of each patient was 20-30 min. All the
ultrasound examinations were performed without knowledge of the laboratory findings of the patients. The time interval between the sampling of blood or urine for laboratory examination and ultrasound examination was less than 3 days. Resistive index, renal length, renal cortical echogenicity, and the degree of cortico-medullary contrast were compared with serum creatinine level, and the statistical significances of those correlations were evaluated by t-test. In patients with a normal level of serum creatinine, we evaluated the correlation between resistive index and albuminuria (albustix-positive) using Wilcoxon rank sum test. In 23 patients for whom the data for creatinine clearance were available, resistive index was compared with creatinine clearance level using a regression analysis.
Fig. l(b). For legend, see p. 78.
78
Fig. 1. Duplex Doppler sonograms of the kidney in patients with diabetes mellitus. (a) A 45-year-old female patient with a history of diabetes mellitus for 7 years being managed by oral medications. The Doppler spectrum obtained in the region of an arcuate artery shows prominent continuous antegrade flow throughout the diastolic phase with a resistive index of 0.722. Her serum creatinine level was 88.4 pmol/l (1 .O mg/dl) and creatinine clearance was 58 ml/min. Doppler spectral analysis was performed on the spectrum below the baseline. (b) A 69-year-old female patient with a history of diabetes for 10 years being managed by self injection of insulin for 4 years. The Doppler spectrum obtained in the region of an interlobar artery shows diminished, but still continuous, antegrade flow throughout the diastolic phase with a resistive index of 0.777. Her serum creatinine level was 344.8 pmol/l (3.9 mg/dl) and creatinine clearance was 10 ml/n% (c) A 52-year-old male patient with a history of diabetes for 10 years being managed by oral medications. The Doppler spectrum obtained in the region of an interlobar artery shows complete loss of enddiastolic flow, resulting in a resistive index of 1.0. His serum creatinine level was 556.9 pmol/l (6.3 mg/dl) and creatinine clearance was 12 ml/min.
Results There were 18 patients with a normal serum creatinine level (< 1.4 mg/dl) and 14 patients with an elevated serum creatinine level (> 1.4 mg/dl) up to 13.7 mg/dl. Resistive indices of Doppler spectra obtained from arcuate or interlobar arteries of the kidneys of patients with a normal serum creatinine level were between 0.56 and 0.82 with a
mean of 0.69 (Fig. la). In patients with an elevated serum creatinine level, resistive indices were between 0.72 and 1.0 with a mean of 0.92 (Fig. lb,c). There was a statistically significant difference between resistive indices in diabetic patients with a normal serum creatinine level and those in diabetic patients with an elevated serum creatinine level (P~0.05) (Fig. 2). If we use a resistive index of 0.75 as a cut-off value for pre-
79
DM Nephropathy Serum creatinine
DM Nephropathy
vs Resistive Index
Creatinine Clearance vs Resistive Index 100
.
90. r 'E 3 ig 8 6 f" 0 0 .5 5 s! 6
90--
*..A
A .A
70- .... 60.
a--
*;_ AA
*
*r.&A...
m_
A. *
20.
* ;..
IO-OT 0.5
0.6
0.7
0.8
0.9
1
1.1
Fmidive Index
Fig. 2. Serum creatinine versus resistive index in patients with diabetes mellitus. As the serum creatinine level increases, resistive index also increases.
Fig. 3. Creatinine clearance versus resistive index in patients with diabetes mellitus. As the creatinine clearance decreases, resistive index increases.
dieting an abnormal serum creatinine level, it has a sensitivity of 93 %, a specificity of 83 %, an accuracy of 88 %, a positive predictive value of 8 1%) and a negative predictive value of 94% (13 truepositives, three false-positives, 1.5 true-negatives, and one false-negative). In 23 patients for whom data of creatinine clearance were available, the resistive index also correlated well with creatinine clearance level on regression analysis with a correlation coefficient of -0.828, which was statistically significant at the 95% confidence level (Fig. 3). Among 18 patients with a normal serum creatinine level, urine albumin was positive in four patients and negative in 14 patients. In 14 patients with normal serum creatinine and negative urine albumin, resistive indices were between 0.56 and 0.81 with a mean of 0.68. In four patients with a normal serum creatinine level and positive urine albumin, resistive indices were between 0.70 and 0.82 with a mean of 0.75. In those diabetic patients with a normal serum creatinine level, there was no statistically significant difference between resistive index in patients with negative urine albumin and resistive index in patients with postive urine albumin (P = 0.16). The cortical echogenicity of the renal cortex was normal (grade 0) in 17 patients and equal to that of the liver (grade 1) in 15 patients. There
was no case for whom renal cortical echogenicity was higher than that of the liver. The serum creatinine level in patients with normal cortical echogenicity was 1.27 + 0.95 mg/dl (mean + one standard deviation) and 4.96 +_3.42 mg/dl in those for whom the cortical echogenicity was equal to that of the liver. There was a statistically significant difference between the serum creatinine level of patients with normal renal cortical echogenicity and those of patients with increased cortical echogenicity (P~0.05). If we regard an abnormal renal cortical echogenicity as a sign of abnormal serum creatinine level, it has a sensitivity of 86 %, a specificity of 83 %, an accuracy of 84%, a positive predictive value of SO%, and a negative predictive value of 88% (12 truepositives, three false-positives, 15 true-negatives, and two false-negatives). There was no case in which corticomedullary contrast was abnormally enhanced (grade 3) or completely obliterated (grade 0). In 14 cases, corticomedullary contrast was normal (grade 2) and in 18 cases corticomedullary contrast was poorly present (grade 1). When we compared the corticomedullary contrast and serum creatinine level, there was no statistically significant correlation. The average length of both kidneys was between 9.2 and 13.3 cm with a mean of 10.7 cm. In patients in whom serum creatinine was nor-
80
DM Nephropathy Serum creatinine vs Kidney Length
Fig. 4. Serum
creatinine
was no significant
versus
correlation
length
between
and kidney
of the kidney. serum
creatinine
There level
length.
mal, renal length was 10.85 + 0.88 cm, and it was 10.49 k 0.97 cm in patients with abnormal serum creatinine. There was no significant correlation between the length of the kidney and serum creatinine level in patients with diabetes mellitus (P = 0.28) (Fig. 4).
Discussion The kidney is involved in diabetes mellitus in different ways, including diabetic intercapillary glomerulosclerosis, arteriosclerotic changes, glycogen accumulation in the renal tubular epithelium, and acute and chronic pyelonephritis [ 1,4]. Thickening of the basement membranes of the glomerular capillaries and mesangial expansion, which in association with arteriosclerotic changes, may increase renal vascular resistance. These changes in structure are already present very early in the course of diabetic kidney disease and manifest clinically as renal hypertrophy, glomerular hyperfiltration, and sometimes microalbuminuria. In the late stage of the disease, overt (dipstick-positive) proteinuria appears and the patient falls into end-stage renal failure [ 11. It has been reported that diabetes mellitus is one of the numerous causes of bilaterally enlarged kidneys. Excessive glycoprotein deposition result-
ing in enlargement of the glomeruli and the presence of a renotrophic factor such as growth hormone are suggested as possible causes of the renal enlargement in diabetes mellitus [2,3]. However, to our best knowledge, there has been no radiological report written in English regarding the sonographic or Doppler spectral criteria which can predict the functional status of the kidneys in a patient with diabetes mellitus. In our study, renal length was compared with serum creatinine level, and there was no significant correlation between the size of the kidney and the functional status of the kidney. There was a poor correlation between the degree of corticomedullary contrast on ultrasound images and serum creatinine level. Although it has generally been considered that renal cortical echogenicity is neither sensitive nor specific for renal disease [ 71, a few reports opposed that opinion. Rosenfield and Siegel reported that there was a definite relation between cortical echogenicity and the severity of interstitial changes on renal biopsy [ 61. In another report by Choyke et al., renal cortical echogenicity correlated well with severity of the disease in patients with hemolytic uremic syndrome [ 81. In our study, renal cortical echogenicity was a relatively accurate index of the functional status of the kidney in patients with diabetes mellitus. Recently, duplex Doppler sonography has been used in native kidneys with medical renal diseases with promising results [ 9-131. In a report by Patriquin et al., they illustrated an excellent correlation between intrarenal Doppler spectral changes and clinical course of their patients with hemolytic-uremic syndrome [ lo]. This excellent correlation could be explained by the fact that underlying renal changes in hemolytic-uremic syndrome consist of vascular lesions that include microvascular thrombosis and endothelial swelling, which directly affects the degree ofrenal blood flow impairment. Likewise in diabetic kidneys, main pathologic changes affect the circulatory apparatus of the kidney, the glomerular and peritubular capillaries, the arterioles of the glomerulus, and the medium and small arteries of the kidney. Those pathologic changes include intercapillary
81
glomerulosclerosis and arteriosclerotic changes. Doppler spectral changes in a diabetic patient probably reflect the status of the intrarenal blood flow and glomerular filtration. Resistive index is a commonly used angleindependent index representing peripheral vascular impedance [ 131. When the end-diastolic flow signal is absent, the resistive index is 1.0. If the direction of the end-diastolic flow is reversed, the resistive index becomes greater than 1.0. Recently, the primary authors of this article have reported a positive correlation between resistive index and serum creatinine level in patients with medical renal disease and in normal controls [ 131, in which the resistive index of the normal control group was 0.627 & 0.042. Proteinuria is regarded as one of the bad prognostic signs in patients with diabetes mellitus [ I] _ Although in our study resistive index in patients with a normal serum creatinine level and negative urine albumin was not significantly different from that in patients with a normal serum creatinine level and positive urine albumin, further study will be necessary in this respect. In conclusion, analysis of the Doppler spectrum of the intrarenal arteries in conjunction with careful evaluation of the renal cortical echogenicity might be helpful in sonographic differentiation of kidneys with preserved function and those with impaired function in patients with diabetes mellitus.
References 1 Morgensen, C.E., Mauer, S.M. and Kjellstrand, C.M. (1988) Diabetic nephropathy. In: R.W. Schrier and C.W.
2
3 4
5
6
7
8
9
10
11 12
13
Gottschalk (Eds.), Diseases of the Kidney, 4th edn., Vol. 3. Little, Brown and Company, Boston. MA, pp. 2395-2431. Segel, M.C., Lecky, J.W. and Slasky, B.S. (1984) Diabetes mellitus: the prominent cause of bilateral renal enlargement. Radiology 153, 341-342. Kahn, C.B., Raman, P.G. and Zic. Z. (1974) Kidney size in diabetes mellitus. Diabetes 23. 788-792. Jones, D.B. (1985) Kidneys. In: J.M. Kissane (Ed.), Anderson’s Pathology, 8th edn., Vol. 2, C.V. Mosby, St Louis, MO, pp. 754-755. Hricak, H., Cruz, C., Romanski, R. et al. (1982) Renal parenchymal disease: sonographic-histologic correlation. Radiology 144. 141-147. Rosenfield. A.T. and Siegel, N.J. (198 1) Renal parenchyma1 disease: histopathologic-sonographic correlation. AJR 137, 793-798. Platt, J.F.. Rubin, J.M., Bowerman, R.A. and Marn, C.S. (1988)The inability to detect kidney disease on the basis of echogenicity. AJR 151, 317-319. Choyke, P.L., Grant, E.G.. Hoffer, F.A., Tina. L. and Korec, S. (1988) Cortical echogenicity in the hemolytic uremic syndrome: clinical correlation. J. Ultrasound Med. 7, 439-442. Wong. S.N., Lo, R.N.S. and Yu, E.C.L. (1989) Renal blood flow pattern by noninvasive Doppler ultrasound in normal children and acute renal failure patients. J. Ultrasound Med. 8, 135-141. Patriquin. H.B., O’Regan, S., Robitaille, P. and Paltiel, H. (1989) Hemolytic-uremic syndrome: intrarenal arterial Doppler patterns as a useful guide to therapy. Radiology 172, 625-628. Keller, M.S. (1989) Renal Doppler sonography in infants and children. Radiology 172, 603-604. Platt, J.F., Ellis, J.H., Rubin, J.M., DiPietro, M.A. and Sedman, A.B. (1990) Intrarenal arterial Doppler sonography in patients with nonobstructive renal disease: correlation of resistive index with biopsy findings. AJR 154, 1223-1227. Kim, S.H., Kim, W.H., Choi, B.I. and Kim, C.W. (1992) Duplex Doppler US in patients with medical renal disease: resistive index vs serum creatinine level. Clin. Radiol. 45. 85-87.
